DESCRIPTION: The fact that more than 500,000 patients in the United States died from cancer in 1997 indicates that cancer, in its many forms, is still largely incurable and underscores the importance of focusing new treatments and research, at least in pat on optimizing the management of cancer pain. The greatest obstacle to developing new treatments for cancer pain and/or optimally coordinating existing treatments is a paucity of knowledge defining the neurobiology of cancer pain. We have recently developed two animal models of tumor allodynia and hyperalgesia, which we believe will be useful in developing an understanding of the basic mechanisms of cancer pain. In the studies proposed below in vivo microdialysis be utilized to analyze the baseline levels and stimulated release of substance P and putative allogens within a bone tumor and a soft tissue tumor model Weal pursue the following Specific Aims: 1. To measure the basal release of the substance P, PGE.2, endothelin-1, nerve growth factor, and the c$o&ines, TNF-a and IL-1 at tumor sites at several time points as compared to comparable sites in control animals. We will also measure the release of the above substances at the tumor site during peripheral nerve activation. 2. To ascertain whether the tumor cells or accessory cells (such as osteoclasts) at the tumor site are producing the mediators measured by microdialysis in Specific Aim 1. This aim will utilize immunocytochemistry to localize the protein for each algogen at the tumor sites. 3. To determine if the administration of tumor-associated mediators can mimic, and their antagonists reduce, the nociceptive responsiveness in behavioral pain tests. To our knowledge the proposed experiments are the first to utilize the technique of microdialysis to directly measure substances produced and released in vivo by a tumor in awake, freely moving animals aver time. The results should provide important, new data regarding the mediators released in vivo by soft tissue and bone tumors and will dramatically advance knowledge in the area of the neurobiology of cancer pain.